TP53 mutations in workers exposed to occupational carcinogens

Abstract

For the p53 Special IssueIn some cases, evidence exists that exogenous carcinogenic exposures contribute to the mutation spectrum of the TP53 gene (p53) in human cancers. Although the clearest examples come from dietary and environmental sources, only a restricted number of papers have concentrated specifically on TP53 mutations in tumors from workers exposed to occupational carcinogens. In populations exposed to dietary aflatoxin B1 with liver cancer (AFB1) and ultraviolet (UV)-radiation with skin cancer, a single specific-looking TP53 mutation has been described in some of the tumors. Whether these fingerprints in the TP53 gene can be used to reveal an occupational etiology remains to be shown. In other cases, although differences in the TP53 mutation spectrum exist, they are more diffuse and difficult to interpret at this point. For instance, cigarette smoking seems to induce long-lasting molecular footprints in TP53. However, their use to rule out other occupational exposures as etiological factors in occupational cancers is still very questionable, especially due to the putative synergistic effects of cigarette smoke with other carcinogens. Although interesting implications of possible typical mutation spectra among cancers with other occupational etiologies exist, the data are scanty and await further development of TP53 mutation databases. Hum Mutat 21:240-251,

Missense Mutations of MADH4

“…For example, missense mutations within pancreatic cancers predominantly occur within the MH1 domain or the MH2 domain COOH-terminal to the MCR, whereas those mutations affecting gastrointestinal mucosa (small bowel or colorectal carcinomas) occur more frequently within the MCR. Tumor type clustering of mutations as a function of environmental influences is a recognized phenomenon of other genes known to be important in carcinogenesis, such as p53 and K-ras (48,49). Thus, differential influences may exist that contribute to the mutational spectrum of MADH4.…”

Genetic Single Nucleotide Polymorphisms (GSNPs) in the DNA Repair Genes and Hepatocellular Carcinoma Related to Aflatoxin B1 among Guangxiese Population

“…Furthermore, AFB1-N 7 -Gua and AFB1-FAPy can induce error-prone DNA repair and result in the damage of DNA strands, including double-strand breaks (DSBs), single-strand breaks (SSBs), base pair substitution, frame shift mutations, and oxidation DNA damage such as 8-oxodeoxyguanosine (8-oxyG) [25][26][27][28]. For genes mutations induced by AFB1 exposure, G:C > T:A mutation in codon 249 of TP53 gene has been frequently reported [29][30][31][32][33][34][35][36]. This mutation is tested in more than 40% of HCC from high-AFB1-exposure areas, but in either very rare or absent for those from low or null AFB1 exposure areas [36][37][38][39].…”

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

“…Recent studies have shown that the levels of AFB1-DNA adduct of the peripheral blood white cells are positively and lineally correlated with that of liver cells, implying analysis of AFB1-DNA adducts in the peripheral blood white cells may substitute for the elucidation of tissular levels of adducts (39,41). For genes mutations induced by AFB1 exposure, the experimental and theoretical researches are briefly on the p53 gene (42)(43)(44)(45)(46)(47)(48)(49). Reaction with DNA at the N 7 position of guanine preferentially causes a G:C > T:A mutation in codon 249 of this gene, leading to an amino acid substitution of arginine to serine (44)(45)(46)(47)(48)(49)(50).…”

“…For genes mutations induced by AFB1 exposure, the experimental and theoretical researches are briefly on the p53 gene (42)(43)(44)(45)(46)(47)(48)(49). Reaction with DNA at the N 7 position of guanine preferentially causes a G:C > T:A mutation in codon 249 of this gene, leading to an amino acid substitution of arginine to serine (44)(45)(46)(47)(48)(49)(50). In high AFB1-exposure areas, this mutation is present in more than 40% of HCC and can be detected in serum DNA of patients with preneoplastic lesions and HCC (41).…”